The Proteomics Core Facility at the University of Kentucky (UK) College of Medicine requests $416,290 to acquire a matrix-assisted laser desorption ionization (MALDI) tandem time-of-flight (TOF/TOF) mass spectrometer. The goal of this application is to provide advanced mass spectrometry capabilities to meet the proteomics needs of 18 highly productive NIH-funded investigators at UK. Compared to an older model, the Applied Biosystems 4800 MALDI-TOF/TOF mass spectrometer offers 10x better sensitivity, enhanced precursor ion selection, and more efficient fragmentation of singly charged precursor ions generated by MALDI using high energy (2 KeV) collision-induced dissociation. Its superior mass accuracy and resolution in both MS and tandem MS/MS modes enable powerful proteomics capabilities. This equipment will provide state-of-the- art capabilities to the Proteomics Core Facility and enhance the ability of the facility to meet an ever-increasing volume and intensity of research support. This equipment is essential to these ongoing research programs and to stimulating and enabling new collaborative research initiatives on protein identification, posttranslational modification characterization, gene discovery, and functional proteomics. Currently, there is no MALDI- TOF/TOF mass spectrometer at UK or any universities in the Commonwealth of Kentucky. The purchase of the MALDI-TOF/TOF mass spectrometer is critical to the continuing expansion and enhancement of the proteomics research program in human disease and basic research at UK. As described in this application, 18 NIH-funded investigators from 10 different departments have specific needs for this mass spectrometer, which will be a shared research resource. Indeed, due to the lack of a more sensitive and high throughput MALDI- TOF/TOF mass spectrometer on campus and the current usage saturation of the other instruments, some of these research projects are seriously delayed or compromised. Thus, the purchase of the MALDI-TOF/TOF mass spectrometer will have a major impact on research capabilities at our institution. Relevance The research to be supported by this instrument spans a wide spectrum of biological and biomedical research, including cutting-edge programs focused on neurological disorders such as Alzheimer's disease, Parkinson's disease and Lou Gehrig's disease; cancer biology including DNA repair, gene regulation and apoptosis in prostate, breast and skin cancers; and diabetes and cardiovascular disease. Other programs explore fundamental questions in signaling pathways and gene transcription regulation that are critical to the pathogenesis of multiple major diseases such as cancer, diabetes and neurological disorders or study the role of metalloproteases in ovarian function and women's health. The addition of this instrument to the Proteomics Core Facility at UK Medical Center will significantly enhance the productivity and progress of these research programs, thus advancing the NIH mission to improve public health. [unreadable] [unreadable] [unreadable]